tbuckley/cabot-search huggingface dataset:
Evaluation of social connectedness, loneliness, and anxiety among cancer survivors during the 2020-2021 winter surge of COVID-19 pandemic.
Authors: Hermine Poghosyan, James B. Yu
Journal: Journal of Clinical Oncology (2022)

12061 Background: Limited research is available about cancer survivors’ level of stress, social connectedness and loneliness during the COVID-19 that can put them at increased risk for poor physical and mental health. We estimated relative decreased rate of social connectedness and increased rates of loneliness/sadness and stress/anxiety among cancer survivors during the 2020-2021 winter surge of COVID-19 and investigated whether decreased social connectedness is associated with increased feelings of loneliness/sadness and stress/anxiety. Methods: This cross-sectional study used data from Medicare Current Beneficiary Survey COVID-19 Winter 2021 Supplement, nationally representative phone survey of Medicare beneficiaries living in community, conducted in March-April 2021. We included 1,836 respondents who self-reported cancer history (other than skin cancer). Outcomes were self-reported feelings of loneliness/sadness and stress/anxiety over the past 4 months. The independent variable was social connectedness defined as feeling less socially connected to family/friends over the past 4 months. We used weighted descriptive statistics and multivariable logistic regression adjusting for self-reported socio-demographics (age, sex, race, income), region, metropolitan residency, Medicaid eligibility, living alone, depression, having access to internet and health care. We applied sample weights to account for complex survey design with results generalizable to 9.5 million cancer survivors. Results: Out of 9505626 cancer survivors, 6.8% self-reported as Black, 7.1% Hispanic, 80.4% White, 59% women, 42.7% reported decreased social connectedness, 20.3% increased feeling of loneliness/sadness, and 40.0% increased feeling of stress/anxiety in the past 4 months. Women had higher rates of reporting increased feelings of loneliness/sadness (12.0% vs. 26.1%, P = &lt;.001), stress/anxiety (30.0% vs. 46.6%, P = &lt;.001), and decreased social connectedness (38.7% vs. 45.5% P =.028) than men in the past 4 months. Among self-reported racial and ethnic groups, Hispanics had the highest rates of reporting increased feelings of loneliness/sadness (31.2% vs. 20.5% of Whites vs. 10.2% of Blacks, P =.008) and stress/anxiety (54.0% vs. 39.4% of Whites vs. 31.2% of Blacks, P =.034). No statistically significant difference was found in social connectedness by self-reported race and ethnicity. Survivors who reported decreased social connectedness had higher odds of feeling more lonely/sad (adjusted OR = 3.67, 95%CI 2.85-4.72, P = &lt;.001) and more stressed/anxious (adjusted OR = 2.63, 95%CI 2.1- 3.26, p = &lt;.001) over the past 4 months. Conclusions: Increased feelings of loneliness/sadness and anxiety/stress in the past 4 months were prevalent among cancer survivors. Also, almost half of them reported decreased social connectedness at the end of the second year of COVID-19.
FLOT neoadjuvant therapy turns the expression patterns of cancer cells similar to those of non-cancer cells in gastric cancer patients.
Authors: Williams Fernandes Barra, Jessica Costa Silva, Ronald Matheus da Silva Mourao, Ana Karyssa Anaissi, Samia Demachki, Geraldo Ishak, Danielle Queiroz Calcagno, Fabiano Cordeiro Moreira, Paulo Pimentel Assumpção
Journal: Journal of Clinical Oncology (2022)

e16056 Background: FLOT perioperative have emerged as a new standard for locally advanced gastric cancer (LAGC). Nevertheless, the molecular consequences of such therapy remain obscure. Aiming to investigate changes in the tumor transcriptional landscape in LAGC patients treated with FLOT, a comprehensive analysis of messenger RNA (mRNAs) and long noncoding RNA (lncRNAs) expression was developed using next-generation sequencing (NGS). Methods: Paired tumor and non-tumor fresh samples, including 17 patients with intestinal-type LAGC submitted to neoadjuvant FLOT treatment (treated group) and 13 who did not receive neoadjuvant therapy (untreated group), were sequenced and compared. Differential expression analyses were performed using the DESeq2 package. Criteria for differentially expressed (DE) lncRNAs and mRNAs were|Log2(Fold-Change)| &gt; 2; and adjusted p-value &lt; 0.05. In silico analyses were adopted to identify DE lncRNAs with transcription factors (TFs) and RNA-binding proteins (RPBs). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and gene ontology (GO) was also performed to elucidate these target proteins’ and mRNAs biological’s roles. Results: In tumor samples from the untreated group, 4443 mRNAs and 961 lncRNAs DE were found, in which 293 mRNAs and 148 lncRNAs accurately discriminated (the area under the curve ROC &gt; 0.9) tumor and non-tumor tissues. Only 265 mRNAs and 29 lncRNAs DE were detected in treated patients, indicating that neoadjuvant therapy led to changes in expression patterns, making tumor tissues similar to non-tumor tissues. Subsequent analyzes identified that non-tumor tissues (treated vs. untreated) showed similar expression profiles. Among tumor samples, 34 mRNAs and 54 lncRNAs DE were found, in which 7 mRNAs and 16 lncRNAs can discriminate between treated and untreated tumors, indicating the effect of neoadjuvant treatment is predominant in the tumor. GO evaluation of genes was significant for 83 terms for biological process. The most annotated terms were the regulation of catalytic activity. We also observed that DE lncRNAs interact with TFs and RBPs were enriched in related cancer development and progression pathways, including transcriptional dysregulation and cellular senescence. Conclusions: Despite the need for further validation to better understand the transcriptional landscape related to neoadjuvant treatment, the present study highlights the functional relevance of lncRNAs in tumor biology and, mainly, shed light on the molecular effects of FLOT neoadjuvant treatment, that might help to guide future investigations aiming to establish personalized management of GC.
Safety and efficacy of daratumumab use in patients with renal impairment and hemodialysis.
Authors: Mateusz Niewinski, Jamie Chin-Hon, Meredith Akerman, Faith Davies, Gareth Morgan, Marc Justin Braunstein
Journal: Journal of Clinical Oncology (2022)

8026 Background: Targeting CD38 in multiple myeloma (MM) using daratumumab-based regimens can prolong remission in both the newly diagnosed and relapsed settings. However clinical trials have excluded patients with creatinine clearances (CrCl) &lt;30 mL/min, warranting real-world analysis of daratumumab use in MM patients with renal insufficiency. Methods: Following IRB approval, we performed a retrospective chart review of relapsed MM patients at our institution who had reduced CrCl and received at least one dose of either daratumumab between October 2018 and January 2022. All subjects received IV daratumumab, 52% went on to receive SQ. Outcomes included change in CrCl during treatment, adverse events, and survival. Survival was estimated using product-limit estimates. CrCl groups at daratumumab initiation of more or less than 30 were compared using the chi-square test or Fisher’s exact test, as deemed appropriate, for categorical variables and the two-sample t-test or Mann-Whitney test for continuous data (SAS Institute Inc., Cary, NC). Results: 101 MM patients were included, with median age of 74 (54-92); 46 (45.5%) were female. 14% were on hemodialysis. Patients had a median of 2 prior lines of therapy. Distribution of R-ISS stages were I (20%), II (35%), and III (45%). High-risk cytogenetics were present in 20%. A median of 23 daratumumab infusions (1-60) were delivered over a median of 18 months (median IV=16, SQ=10). Daratumumab regimens included DRD (32%), DPD (35%), DKD (13%), and DVD (35%). Median CrCl at MM diagnosis and at daratumumab initiation was 45 (7.3-101) and 40 (5.3-107), respectively, with 33% having CrCl &lt;30. Following 3, 6, and 12 months (n = 95, 89, 69) on daratumumab-based regimens, median CrCl were 45, 43, and 41, respectively. There were no differences in renal function in patients who went on to receive SQ daratumumab. 16 patients had died at the time of data collection, and the median survival was 63 months. Of the 101 patients, 16 subjects were deceased at the time of data collection, and 23% of subjects had gone on to subsequent treatments. Analysis showed that there was a progression-free survival of 54% at 5 years. The most common adverse events reported were anemia (37%) and neutropenia (15%). Infusion-related reactions were reported in 19% of patients. Conclusions: This is the largest real-world assessment of outcome for MM patients treated with daratumumab-containing regimens in the setting of renal insufficiency. There was no significant impact of the treatment on renal function at 12 months. Compared to published data on patients treated with CrCl&gt;30, there does not appear to be a detriment to survival or an increase in adverse events when using daratumumab regimens in patients with more advanced renal insufficiency.
Lethality of lung cancer in southeast of Brazil: Real-world data.
Authors: Sabina B. Aleixo, Narelle Parmanhane, Jose Zago Pulido
Journal: Journal of Clinical Oncology (2022)

e22515 Background: Lung Cancer (LC) is one of the most common neoplasm of all malignant tumors, with an increasing lethality and incidence, corresponding to 13.5% of all types of cancer. The world estimate for 2020 was 19 million cases of cancer worldwide, with 10 million deaths of which lung cancer represented 18% of the deaths. It is estimated that in Brazil, according to INCA (National Cancer Center of Brazil) that in the year 2022 there will be 30,200 new cases, the second most common among men and the fourth among women. Unfortunately most cases are diagnosed in late stages and have low survival. Methods: Retrospective study of data from SisRHC (brazilian cancer registry system) of patients diagnosed with LC, treated at the reference cancer center Hospital Evangélico de Cachoeiro de Itapemirim/ES, from January 1, 2010 to December 31, 2019. Results: A total of 440 patients were included and their main characteristics at diagnoses was advanced stages (73.2% III/IV) and only 58 % where able to receive first line treatment: chemotherapy concomitantly with radiotherapy (22,3%), isolated chemotherapy (21.4%) and isolated radiotherapy (14.6%). After first line treatment outcome status was death (49.4%) and disease progression (12.3%). Median survival was 10.3 months. Conclusions: Despite the limitations of the retrospective study these data are important for understanding the pattern of disease in a developing country where acess to health is limited. Unfortunately the barrier of 12 months survival common in developed nations is still not a brazilian reality. Public policies are necessary for improvement
Epidemiological and clinical characteristics of patients with cervical cancer and their care pathway in Rio de Janeiro, Brazil.
Authors: Isabel M Emmerick, Lara Vinhal Faria, Debora Castanheira, Elaine lazzaroni Moraes, Mario Jorge Sobreira da Silva
Journal: Journal of Clinical Oncology (2022)

e18512 Background: Cervical cancer (CC) is one of the most common cancers in Brazil. This study analyzes the epidemiological and clinical characteristics of CC patients from 2012 to 2017 and their care pathway in Rio de Janeiro, Brazil, considering the municipal and state regulations. Methods: Retrospective study using interrupted time series, including women registered in the Hospital Cancer Registry from January 2012 to December 2017. The interventions analyzed were the implementation of the municipal (August 2013) and state (June 2015) regulation for the treatment of CC in Rio de Janeiro. The main outcomes were (A) Individuals from the metropolitan region I (%); (B) referred by the public sector (%); (C) Group I or II staging (%) (D) Patients who received surgery as first treatment (%) (E) positive outcome (%). Results: 3,460 women were included, 71% were 30 to 59 years old. (A) Individuals from the metropolitan region I accounted for over 68% of the patients, with a statistically decrease after municipal regulation and an increase after state regulation. (B) The public sector referred more than 85% of patients by the end of the period, and despite less than 60% of patients diagnosed with stage I and II (C) the percentage of surgery (D) and positive outcomes (E) were increased over time. Conclusions: Municipal and state regulations organized the flow of patients nevertheless is important to invest in infrastructure to increase early detection, aiming to improve equity of access.[Table: see text]
Single-agent neoadjuvant immunotherapy of PD-1 antibody in resectable mismatch repair-deficient/microsatellite instability-high colorectal cancer.
Authors: Jun Huang, Fengyun Pei, Jingjing Wu, Yandong Zhao, Wan He, Tianhao Shi, Meijin Huang
Journal: Journal of Clinical Oncology (2022)

e15605 Background: PD-1 blockade has been recommended as first-line therapy for non-resectable or metastatic mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) colorectal cancer (CRC). However, the safety and efficacy of neoadjuvant immunotherapy of PD-1 blockade for resectable dMMR/MSI-H CRC remains unclear. Methods: From June 2020 and March 2021, eight resectable dMMR/MSI-H CRC patients treated in the 6th Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) were enrolled. All patients accepted 6 doses (200mg/dose, every 3 weeks) of Sintilimab injection (Innovent, LTD) before radical laparoscopic resections. The clinical and pathological data of the 8 patients was analyzed retrospectively. Results: All patients were confirmed dMMR by immunohistochemistry (IHC). However, 87.5% (7/8) of the patients were confirmed MSI-H and 12.5% (1/8) was confirmed microsatellite stable (MSS) by NGS. After 6 doses of neoadjuvant anti-PD-1 therapy, 87.5% (7/8) of the patients achieved pathological complete response (pCR), and the 7 patients were confirmed both dMMR and MSI-H. The rest 12.5% (1/8) who achieved major pathological response (mPR), with residual tumor &lt;1%, was dMMR but MSS. None of the patients had immunotherapy-related adverse events (irAE) of grade 3 or above (CTCAE; version 5.0). 75.0% (6/8) of the patients had grade 1/2 irAE. No operational mortality or complications were found within 30 days after surgery. Conclusions: Single-agent neoadjuvant immunotherapy of PD-1 antibody was safe and effective in resectable dMMR/MSI-H CRC. Double confirmation of both dMMR and MSI-H status was necessary before PD-1 blockade therapy in dMMR/MSI-H CRC patients.
Adavosertib in combination with carboplatin in advanced <i>TP53-</i>mutated platinum-resistant ovarian cancer.
Authors: Alaa Embaby, Jill Jacqueline Geenen, Joachim Kutzera, Dick Pluim, Marta I. Lopez-Yurda, Jos H. Beijnen, Alwin Huitema, Petronella Witteveen, Neeltje Steeghs, Gijs van Haaften, Marcel A.T.M. van Vugt, Jeroen de Ridder, Frans Opdam
Journal: Journal of Clinical Oncology (2022)

5516 Background: Ovarian cancer is globally the second most common cause of death among women with gynecologic malignancies. Despite high initial response rates, the overall prognosis of this patient population remains poor. The majority of advanced ovarian cancers will become platinum resistant defined by recurrence within six months after completion of platinum therapy. In the first part of the current phase II study, the combination of carboplatin and the Wee1 inhibitor adavosertib (AZD1775), showed to be safe and effective in patients with TP53 mutated platinum resistant ovarian cancer. The aim of this additional cohort is to gain more information about the safety and efficacy of the combination and to explore predictive biomarkers for resistance and response to adavosertib. Methods: In this additional cohort 29 evaluable were treated with carboplatin AUC 5 mg/ ml·min and adavosertib 225 mg BID for 2.5 days in a 21-day cycle. The anti-tumor activity was assessed according to RECIST 1.1. Pre-, on- and post-treatment biopsies were obtained to explore genetic determinants of drug resistance and response to adavosertib. Results: A total of 32 patients with a median age of 62 years (39-77 years) were enrolled in this cohort. All patients had carboplatin/paclitaxel as first line therapy. Six patients received a second-line non-platinum containing regimen. Median platinum free interval was 5.8 months (range 1.7 – 11.9). Twenty-nine patients were evaluable for efficacy. Grade 1-2 bone marrow toxicity, nausea, vomiting and fatigue were the most common adverse events. Dose reductions of carboplatin and/or adavosertib were made in 15/29 evaluable patients (52%). Dose delays occurred in the majority of patients (76%), mostly due to neutropenia and thrombocytopenia. Twelve patients showed PR as best response, resulting in an ORR of 38% in the intention-to-treat population (95% CI 21%-56%). The median PFS was 5.6 months (range 1.1-32 months, 95% CI 4.2-7.0) and median duration of response was 5.3 months (95% CI 0.13-10.5). Conclusions: Adavosertib 225 mg BID for 2.5 days and carboplatin AUC 5 in a 21-day cycle could be safely combined and shows promising anti-tumor efficacy in patients with platinum resistant ovarian cancer. Bone marrow toxicity remains the most common reason for dose reductions and dose delays. Translational biomarker results (CCNE1 analysis as potential predictive marker for response and resistance and WGS) to better understand the anti-tumor activity of the combination are pending. Clinical trial information: NCT01164995.
Covid-death mean-imputation (CoDMI) algorithm and survival analysis: First clinical application in rectal cancer.
Authors: Francesca De Felice, Luca Mazzoni, Daniela Musio, Vincenzo Tombolini, Franco Moriconi
Journal: Journal of Clinical Oncology (2022)

e15592 Background: We illustrate a clinical application of Covid-Death Mean-Imputation (CoDMI) algorithm in survival analysis. CoDMI algorithm is a new statistical tool that allows to adjust, through mean imputation based on the Kaplan-Meier model, Covid-19 death events in oncologic clinical trials, providing a complete sample of observations to which any statistical method in survival analysis can be applied. Methods: We analyzed a group of patients who received trimodal treatment – neoadjuvant chemoradiotherapy, followed by surgery and adjuvant chemotherapy – for primary locally advanced rectal cancer (LARC). Overall survival (OS) was calculated in months from the date of diagnosis to the first event, including date of last follow-up or death. Because Covid-19 death events potentially bias survival estimation, to eliminate skewed data due to Covid-19 death events the observed lifetime of Covid-19 cases was replaced by its corresponding expected lifetime in absence of the Covid-19 event using CoDMI algorithm. In a traditional Kaplan-Meier approach, patient died of Covid-19 (DoC) can be: i) excluded to the cohort; ii) counted as censored (Cen); iii) considered as died of disease (DoD). CoDMI algorithm offers an additional, more satisfactory option: iv) DoC events are mean-imputed as no-DoC cases at later follow-up times. With this approach, the observed lifetime of each DoC patient is considered as an “incomplete data” and is extended by an additional expected lifetime computed using the classical Kaplan-Meyer model. Results: In total 94 patient records were collected. At the time of the analysis, there were 16 DoD cases, 1 DoC patient and 77 Cen cases. The DoC patient died due to Covid-19 52 months after diagnosis. CoDMI algorithm computed the expected future lifetime (beyond the DoC time of occurrence) provided by the Kaplan-Meier estimator applied to the no-DoC observations as well as to the DoC data itself. Given the DoC event at 52 months, CoDMI algorithm (applied in its standard form: DoC as virtual DoD) estimated that this patient would be died after 79.5 months of follow-up. Table summarizes the 2-year OS and the 5-year OS rates for the different treatment of DoC event. Since our sample contains only one DoC case, the effects on the estimates of the options considered differ very little. In this situation, however, one can better understand how CoDMI algorithm works. Conclusions: CoDMI algorithm leads to the “unbiased” (appropriately adjusted) OS probability in LARC patients with Covid-19 infection, compared with that provided by a naïve application of the Kaplan-Meier approach. This allows a proper interpretation of Covid-19 events in survival analysis. A user-friendly version of CoDMI is available at https://github.com/alef-innovation/codmi.
Activation of the AKT pathway and outcomes in patients (pts) treated with or without ipatasertib (ipat) in metastatic castration-resistant prostate cancer (mCRPC): Next-generation sequencing (NGS) data from the phase III IPATential150 trial.
Authors: Christopher Sweeney, Kim N. Chi, Sergio Bracarda, Cora N. Sternberg, David Olmos, Shahneen Sandhu, Christophe Massard, Nobuaki Matsubara, Malgorzata Nowicka, Nives Selak Bienz, Fanny Schenkel, Geng Chen, Matthew J. Wongchenko, Josep Garcia, Johann S. De Bono
Journal: Journal of Clinical Oncology (2022)

5056 Background: Ipat + abiraterone (abi) significantly reduced the risk of radiographic disease progression vs placebo (pbo) + abi in pts with mCRPC and PTEN loss tumors by immunohistochemistry (IHC; HR, 0.77; 95% CI: 0.61, 0.98; P=0.034) but not in ITT pts (HR, 0.84; 95% CI: 0.71, 0.99; P=0.043; Sweeney Lancet 2021). A greater risk reduction was seen in pts with PTEN loss by NGS (HR, 0.65; 95% CI: 0.45, 0.95). We describe the efficacy and safety of pbo + abi vs ipat + abi at the second interim analysis (IA) of overall survival (OS) and explore the impact of AKT pathway alterations. Methods: Pts with mCRPC were randomized 1:1 to ipat (400 mg/d) + abi (1000 mg/d) + prednisone (5 mg bid) or pbo + abi + prednisone. Coprimary endpoints were investigator-assessed radiographic progression-free survival by Prostate Cancer Working Group 3 (PCWG3) criteria in pts with PTEN loss tumors by IHC (PTEN loss in ≥50% of tumor cells) and in ITT pts. Secondary endpoints in both populations included OS, objective response rate (ORR) per RECIST 1.1 and PCWG3 and time to pain progression (TPP). Ad hoc analyses assessed pts with PIK3CA/ AKT1/ PTEN alterations by NGS vs wildtype (WT). Results: Median follow-up was 31 mo (cutoff: 2021 Sept 30). In PTEN loss by IHC pts, median OS was 35.8 mo (n=261) with pbo + abi and 36.8 mo (n=260) with ipat + abi (HR: 0.95; 95% CI: 0.74, 1.21; P=0.665); in ITT pts, median OS was 36.7 mo (n=554) with pbo + abi and 40.3 mo (n=547) with ipat + abi (HR: 0.90; 95% CI: 0.76, 1.07). With longer follow-up, the safety profile was consistent with that of the primary analysis. In the full NGS evaluable population (n=743), ipat + abi was associated with better outcomes in pts with PIK3CA/ AKT1/ PTEN alterations (Table). Among pts with PTEN loss tumors by NGS (205 of the evaluable 518 pts), median OS was 29.8 mo (n=102) with pbo + abi and 35.8 mo (n=103) with ipat + abi (unstratified HR: 0.82; 95% CI: 0.56, 1.19). Conclusions: At the second IA, no significant improvement in OS was observed with ipat + abi in pts with PTEN loss by IHC. Exploratory analyses in pts with PIK3CA/ AKT1/ PTEN alterations by NGS suggest that these patients have poorer prognosis but may derive greater benefit from ipat + abi. Clinical trial information: NCT03072238. [Table: see text]